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Efficacy and Toxicity of Increasing Doses of Idarubicin, Cytarabine and G-CSF in Acute Myeloid Leukemia

Phase 2
Completed
Conditions
Di Novo Acute Myeloid Leukemia
Interventions
Registration Number
NCT01700413
Lead Sponsor
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Brief Summary

While several studies have been reported with increasing doses of daunorubicin in the first line treatment of Acute Myeloid Leukemia (AML), there is no similar experience with idarubicin as initial treatment of AML.

As idarubicin is the most common treatment used for AML, it is needed to find the optimal dose for the combination of idarubicin, cytarabine and G_CSF, to explore if this combination improves the outcomes of current treatments for AML.

The aim of this dose-finding study is to find the optimal dose for the combination of idarubicin, cytarabine and G-CSF that could improve the response rate, reduce relapse and improve survival of patients with primary acute myeloid leukemia. This could be a significant advance in a field where treatment outcomes have stabilized in the last 15 years. This study will be the basis for further prospective, randomized, multicenter trial comparing idarubicin maximum tolerated dose, compared to standard treatment with idarubicin and cytarabine, including raising both arms in G-CSF. The dose of 12 mg/m2 will be administered as control arm in this future randomized study, which will investigate the benefit of enhanced dose identified as optimal in this phase II pilot study.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria

Informed consent signature Patients with newly diagnosed AML, classified according to WHO criteria. Age more than or equal to 18 and less than or equal to 70 years.

Exclusion Criteria

Patients previously treated with chemotherapy for their AML other than hydroxyurea.

Acute promyelocytic leukemia with t (15; 17). Blast crisis of chronic myeloid leukemia. Leukemias that appear after other myeloproliferative neoplasms. Leukemias ensuing myelodysplastic syndromes after more than 6 months. Presence of other malignancies in activity. AML secondary to chemo-radiotherapy treatment for other malignancies. Abnormal renal and hepatic function, with creatinine value and / or bilirubin 2 times the normal limit value, except where the alterations are attributable to leukemia.

Patients with markedly reduced ejection fraction (less than 45%), symptomatic heart failure, or both of the normal value of the center.

Patients with serious concomitant psychiatric or neurological disease. HIV-positive. Pregnancy or breastfeeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
IdarubicinIdarubicinCohort 1: Idarubicin 14 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 2: Idarubicin 16 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 3: Idarubicin 18 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day
Primary Outcome Measures
NameTimeMethod
Rate of complete remissions (CR)From 28 up to 56 days after first induction

Identify the highest dose of idarubicin in combination with cytarabine and G-CSF that produces a CR rate equal to or greater than 65% with tolerable toxicity.

Secondary Outcome Measures
NameTimeMethod
Survival at 9 months from diagnosis9 months after diagnoses

Rate of patients alive at 9 months after diagnosis.

Mortality (as rate) related to study treatmentWeekly during treatment, 3 months after complete remission, 6 months after complete remission and 9 months after complete remission

Causes of death, mortality related treatment, mortality in induction.

Relapse at 6 months6 months from complete remission, expected to be within 9 months from inclusion.

Rate of patients that have relapsed within 6 months after complete remission.

Rate of patients with adverse events as a measure of safety and tolerabilityWeekly during treatment, and on months 3 and 6 after complete response

Hematologic toxicity Gastrointestinal and liver toxicity Cardiac Toxicity Fever and infection Pulmonary complications Duration of hospitalization Mortality and causes of death induction.

Duration of hospitalizationFrom the inclusion until 9 months after inclusion.

Number of days in which the patient is hospitalized.

Trial Locations

Locations (5)

Hospital Universitari Germans Trias I Pujol de Badalona

🇪🇸

Badalona, Spain

Hospital Clinic I Provincial de Barcelona

🇪🇸

Barcelona, Spain

Hospital Clínico Universitario de Valencia

🇪🇸

Valencia, Spain

Hospital de La Santa Creu I Sant Pau

🇪🇸

Barcelona, Spain

Hospitals Vall D'Hebron

🇪🇸

Barcelona, Spain

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